1. Field of the Invention
The invention relates to uses of a sulfur-containing compound. Said sulfur-containing compound has ability to inhibit activities of a factor related to cancer metastasis and/or growth and to inhibit lung cancer metastasis and/or growth.
2. Description of the Related Art
Non-small cell lung cancer (NSCLC) is one of the main causes of cancer death, and its incidence is increasing. Surgery, radiotherapy, and chemotherapy are the major treatment methods to reduce lung cancer mortality (Saba, N. F.; Khuri, F. R. Chemoprevention strategies for patients with lung cancer in the context of screening. Clin. Lung Cancer 2005, 7, 92-99), however, these treatments have harmful side effects on normal healthy cells in the human body. Therefore, it is important to discover new agents to treat lung cancer safely without affecting the body's healthy cells. The deregulation of signaling pathways such as PI3K/Akt is often implicated in the pathogenesis of NSCLC (Li, C. M.; Narayanan, R.; Lu, Y.; Hurh, E.; Coss, C. C.; Barrett, C. M.; Miller, D. D.; Dalton, J. T. 2-Arylthiazolidine-4-carboxylic acid amides (ATCAA) target dual pathways in cancer cells: 5′-AMP-activated protein kinase (AMPK)/mTOR and PI3K/Akt/mTOR pathways. Int. J. Oncol. 2010, 37, 1023-1030). Thus, the need for the accelerated development of effective NSCLC therapies is critical. At present, the design of new therapeutic strategies targeting multiple signaling pathways for more effective disease management in NSCLC is a primary focus of current research.
Overgrowth, invasion, and metastasis are the major characteristics of malignancy with poor clinical outcome. Malignant tumor progression depends upon the capacity to invade, metastasize, and promote the angiogenic host response. The dynamics of extracellular matrix (ECM) remodeling have been the focus of intense investigation for many years. The degradative process is mainly mediated by matrix metalloproteinases (MMPs), which are a family of at least 20 zinc-dependent endopeptidases best known for their ability to hydrolyze ECM components (Man, S.; Gao, W.; Zhang, Y.; Liu, Z.; Yan, L.; Huang, L.; Liu, C. Formosanin C-inhibited pulmonary metastasis through repression of matrix metalloproteinases on mouse lung adenocarcinoma. Cancer Biol. Ther. 2011, 11, 592-598). MMP-9 is expressed in large quantities in the human lung cancer cell line A549 and might play an important role in tumor invasion (Lirdprapamongkol, K.; Kramb, J. P.; Suthiphongchai, T.; Surarit, R.; Srisomsap, C.; Dannhardt, G.; Svasti, J. Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo. J. Agric. Food Chem. 2009, 57, 3055-3063). The activity of MMPs is prone to inhibition by endogenous tissue inhibitor of metalloproteinases (TIMPs), which are specific inhibitors of MMPs, and the imbalance between MMPs and TIMPs may contribute to the degradation or deposition of the ECM (Kodate, M.; Kasai, T.; Hashimoto, H.; Yasumoto, K.; Iwata, Y.; Manabe, H. Expression of matrix metalloproteinase (gelatinase) in T1 adenocarcinoma of the lung. Pathol. Int. 1997, 47, 461-469). Mitogen-activated protein kinases (MAPKs) play an important regulatory role in cell growth, differentiation, apoptosis, and metastasis (Weng, C. J.; Wu, C. F.; Huang, H. W.; Wu, C. H.; Ho, C. T.; Yen, G. C. Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. J. Agric. Food Chem. 2010, 58, 2886-2894). In addition, the phosphatidylinositol-3-kinase/serine/threonine protein kinase (or protein kinaseB)(PI3K/Akt) signal transduction pathway is involved in the development, progression, and metastasis of various tumors (Campbell, I. G.; Russell, S. E.; Choong, D. Y.; Montgomery, K. G.; Ciavarella, M. L.; Hooi, C. S.; Cristiano, B. E.; Pearson, R. B.; Phillips, W. A. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res. 2004, 64, 7678-7681) (Gupta, A. K.; Soto, D. E.; Feldman, M. D.; Goldsmith, J. D.; Mick, R.; Hahn, S. M.; Machtay, M.; Muschel, R. J.; McKenna, W. G. Signaling pathways in NSCLC as a predictor of outcome and response to therapy. Lung 2004, 182, 151-162) (Shih, Y. W.; Chen, P. S.; Wu, C. H.; Jeng, Y. F.; Wang, C. J. Alpha-chaconine-reduced metastasis involves a PI3K/Akt signaling pathway with downregulation of NF-kappaB in human lung adenocarcinoma A549 cells. J. Agric. Food Chem. 2007, 55, 11035-11043).
Taiwan is an island and so us surrounded by the sea. In recent studies, the majority of natural marine products have promising biological activities. Jean et al. (Jean, Y. H.; Chen, W. F.; Duh, C. Y.; Huang, S. Y.; Hsu, C. H.; Lin, C. S.; Sung, C. S.; Chen, I. M.; Wen, Z. H. Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory and analgesic effects of the natural marine compound lemnalol from Formosan soft coral Lemnalia cervicorni. Eur. J. Pharmacol. 2008, 578, 323-331) (Jean, Y. H.; Chen, W. F.; Sung, C. S.; Duh, C. Y.; Huang, S. Y.; Lin, C. S.; Tai, M. H.; Tzeng, S. F.; Wen, Z. H. Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats. Br. J. Pharmacol. 2009, 158, 713-725) showed that natural products isolated from Taiwanese soft corals, such as lemnalol and capnellene, are useful for the treatment of inflammatory diseases in rats. In some studies, the investigation of bioactive marine natural products has led to the isolation of compounds with neuroprotective (Tseng, Y. J.; Wen, Z. H.; Dai, C. F.; Chiang, M. Y.; Sheu, J. H. Nanolobatolide, a new C18 metabolite from the Formosan soft coral Sinularia nanolobata. Org. Lett. 2009, 11, 5030-5032) and anti-inflammatory (Chao, C. H.; Wen, Z. H.; Wu, Y. C.; Yeh, H. C.; Sheu, J. H. Cytotoxic and anti-inflammatory cembranoids from the soft coral Lobophytum crassum. J. Nat. Prod. 2008, 71, 1819-1824) activities from soft corals. In previous studies, dihydroaustrasulfone alcohol produced in vitro anti-inflammatory activity. Wen et al. (Wen, Z. H.; Chao, C. H.; Wu, M. H.; Sheu, J. H. A neuroprotective sulfone of marine origin and the in vivo anti-inflammatory activity of an analogue. Eur. J. Med. Chem. 2010, 45, 5998-6004) showed that dihydroaustrasulfone alcohol not only exhibited in vitro anti-inflammatory activity but also showed potent therapeutic ability in the treatment of neuropathic pain, atherosclerosis, and multiple sclerosis in rats.